A study of the role of Integrin in regulation of mature ostecclast survival

整合素在调节成熟破骨细胞存活中的作用研究

• 批准号: 18592268
• 负责人: OKAMATSU Yoshimasa
• 金额: $ 2.49万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592268/
• 关键词: Osteoclast; Inte erin; Chemotaxis; Chemokine

Osteoclasts (OC) are bone resorbing multinucleated giant cells that are derived from hemopoietic precursors of the monocyte-macrophage lineage. Osteoclasts rapidly undergo apoptosis unless they are stimulated by exogenous mediators, including M-CSF, RANKL. We demonstrated that MIP-1 gamma (CCL9), one of the common chemokine, was stimulated mature osteoclast survival. Chemokines play an important role in immune and inflammatory responses by inducing migration and adhesion of leukocytes, and have also been reported to participate in regulation of several integrin. However, the effect of these integrins and chemokines as survival factor for mature osteoclast remain unclear.In this study, we can get these results until now.1. RANKL-induced mature osteoclast from mouse bone marrow and RAW264.7 cells also up-regulated the expression of integrin beta7 gene using Gene Array and RT-PCR.2. IL-1 AND VtD3-stimulated ST2, mouse osteoblast cell line, expressed several chemokine gene such as CCL7, CCL9 and CCL25 using Gene Array and RT-PCR.3. RAW264.7 cells expressed the several chemokine receptor genes such as CCR2 and CCR9 using RT-PCR.4. CCL9 strongly related to survival of mature osteoclast.5. The osteoclast differentiation was inhibited by anti-integrin a4 antibody and anti-integrin α4β7 antibody, but not anti-integrin β7 antibody and anti-integrin αE antibody.These results suggest that relationship between chemokines and integrins, such as CCL7 (or CCL9) -CCR2 and CCL25-CCR9, participated osteoclast differentiation and osteoclast survival.

破骨细胞（OC）是骨吸收的多核巨细胞，其来源于单核细胞-巨噬细胞谱系的造血前体。破骨细胞迅速发生凋亡，除非它们受到外源性介质的刺激，包括M-CSF，RANKL。我们证明MIP-1 γ（CCL 9），一种常见的趋化因子，刺激成熟破骨细胞的存活。趋化因子通过诱导白细胞的迁移和粘附在免疫和炎症反应中起重要作用，并且还已报道参与调节几种整合素。然而，这些整合素和趋化因子作为成熟破骨细胞存活因子的作用尚不清楚，本研究中，我们得到了这些结果.结论：1.基因芯片和RT-PCR检测结果显示RANKL诱导的小鼠骨髓成熟破骨细胞和RAW264.7细胞整合素β 7基因表达上调。利用基因芯片和RT-PCR技术检测IL-1和VtD 3刺激后小鼠成骨细胞株ST 2表达CCL 7、CCL 9和CCL 25等趋化因子基因。RT-PCR检测RAW264.7细胞表达趋化因子受体基因CCR 2和CCR 9。CCL 9与成熟破骨细胞的存活密切相关.抗整合素α 4抗体和抗整合素α4β7抗体对破骨细胞的分化有抑制作用，而抗整合素β7抗体和抗整合素αE抗体对破骨细胞的分化无抑制作用，提示趋化因子与整合素之间的关系，如CCL 7（或CCL 9）-CCR 2和CCL 25-CCR 9参与了破骨细胞的分化和存活。